The overall aim of the BREATHER trial is to evaluate the role of Short-Cycle Therapy (SCT) in the management of HIV-infected young people who have responded well to antiretroviral therapy (ART) and to determine whether young people with chronic HIV infection undergoing Short-Cycle Therapy of five days on ART and two days off maintain the same level of viral load suppression as those on continuous therapy, over 48 weeks.

To assess the advantages and disadvantages of the strategy, the incidence of toxicities, immunological control, resistance mutations, acceptability, quality of life and adherence to the randomised strategy will also be compared.

Importantly, because of insufficient data on short-term viral load rebound after stopping ART in this population, the trial will incorporate an initial pilot phase in selected centres, to assess the safety of the SCT strategy by evaluating detailed HIV-1 RNA profiles of participants on the SCT strategy.

This outcome measure only considers HIV-1 RNA measurements at these time points due to the difference in viral load monitoring in the pilot phase and the main trial. However if a young person enrolled in the pilot phase has HIV-1 RNA ≥50 copies/ml at weeks 1, 2 or 3 (reproducible on the same sample) or at week 8 (confirmed on the same sample within 1 week), they will be considered as reaching the primary outcome at week 4 and 12 respectively

Continue with current antiretroviral therapy regime as per standard care

Drug: efavirenz

May be taken as 600mg tablet, 200mg tablet or as part of a combination pill

Other Name: Trade name: Sustiva

Experimental: Short Cycle Therapy

Take current antiretroviral therapy 5 days a week (2 days off) as instructed by clinician

Drug: efavirenz

May be taken as 600mg tablet, 200mg tablet or as part of a combination pill

Other Name: Trade name: Sustiva

Eligibility

Ages Eligible for Study:

8 Years to 24 Years (Child, Adult)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

HIV-1 infected young people aged 8 to 24 years inclusive (Young people recruited between the ages of 16-21 must either be in regular physical contact with their clinician or be able to transfer to an adult physician at the same site for follow-up or to an affiliated adult site).

On a stable first-line ART treatment containing at least 2 NRTIs/NtRTIs and EFV for at least 12 months and willing to continue the regimen throughout the study period. Young people on regimens containing nevirapine (NVP) or a boosted protease inhibitor with undetectable viral load for over one year who wish to enrol should switch to EFV. Once they are stable on the EFV containing regimen for more than 12 weeks they may be enrolled (must have 2 subsequent HIV-1 RNA measurements <50 c/ml over a minimum period of 12 weeks). Previous dual therapy and/or substitution of NRTIs is allowed providing any changes were not for disease progression, immunological or virological failure (where virological failure is defined as two successive HIV-1 RNA results>1000 c/ml) subsequent to virological control having been achieved on ART.

Viral suppression (HIV-1 RNA <50 c/ml) for at least the prior 12 months (at least the last 3 measurements, including screening): young people who have experienced a single viral load >50 but <1000 copies/ml (preceded and followed by VL<50 c/ml) in the last 12 months can be enrolled.

Receiving concomitant therapy for an acute illness (young people may be enrolled after finishing therapy).

A creatinine, AST or ALT of grade 3 or above at screening.

On a regimen including nevirapine or a boosted PI (young people may switch to an EFV based regimen).

Previous ART monotherapy (except for the prevention of mother-to-child transmission)

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01641016

Locations

United States, Tennessee

St Jude Children's Research Hospital

Memphis, Tennessee, United States

France

INSERM

Villejuif, France

Germany

Universitätsklinikum Frankfurt

Frankfurt, Frankfurt am Main, Germany, 60596

Ireland

Our Lady's Children's Hospital

Dublin, Ireland

Thailand

Program for HIV Prevention and Treatment (PHPT)/IRD 174

Changklan, Muang, Chiang Mai, Thailand, 50100

HIV-NAT Thai Red Cross AIDS Research Centre

Bangkok, Thailand

Uganda

Joint Clinical Research Centre

Kampala, Uganda

Ukraine

Kiev City AIDS Center

Kiev, Vidpochynku 11, Ukraine, 03115

United Kingdom

Birmingham Heartlands Hospital

Birmingham, United Kingdom

University Hospital Bristol

Bristol, United Kingdom

Leeds General Infirmary

Leeds, United Kingdom

Leicester Royal Infirmary

Leicester, United Kingdom

Evelina Children's Hospital

London, United Kingdom

Great Ormond Street Hospital

London, United Kingdom

Mortimer Market Centre

London, United Kingdom

St George's Hospital

London, United Kingdom

Nottingham University Hospital

Nottingham, United Kingdom

John Radcliffe Hospital

Oxford, United Kingdom

Sponsors and Collaborators

PENTA Foundation

Medical Research Council

French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)